Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
1.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731847

ABSTRACT

Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.


Subject(s)
Antioxidants , Apoptosis , Reactive Oxygen Species , Saponins , Stomach Neoplasms , Humans , Antioxidants/pharmacology , Saponins/pharmacology , Saponins/chemistry , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Cell Line, Tumor , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Anti-Infective Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry
2.
Nano Lett ; 23(15): 6979-6984, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37523860

ABSTRACT

We demonstrate numerically how a spin wave (SW) beam obliquely incident on the edge of a thin film placed below a ferromagnetic stripe can excite leaky SWs guided along the stripe. During propagation, leaky waves emit energy back into the layer in the form of plane waves and several laterally shifted parallel SW beams. This resonance excitation, combined with interference effects of the reflected and re-emitted waves, results in the magnonic Wood's anomaly and a significant increase of the Goos-Hänchen shift magnitude. This yields a unique platform to control SW reflection and transdimensional magnonic router that can transfer SWs from a 2D platform into a 1D guided mode.

3.
Entropy (Basel) ; 25(6)2023 May 27.
Article in English | MEDLINE | ID: mdl-37372202

ABSTRACT

In this paper, we study a two-parameter family of Stieltjes transformations related to holomorphic Lambert-Tsallis functions, which are a two-parameter generalization of the Lambert function. Such Stieltjes transformations appear in the study of eigenvalue distributions of random matrices associated with some growing statistically sparse models. A necessary and sufficient condition on the parameters is given for the corresponding functions being Stieltjes transformations of probabilistic measures. We also give an explicit formula of the corresponding R-transformations.

5.
Article in English | MEDLINE | ID: mdl-36498290

ABSTRACT

INTRODUCTION: Musculoskeletal disorders related to work might be caused by the cumulative effect of occupational exposures during working life. We aimed to develop a new model which allows to compare the accuracy of duration of work and intensity/frequency associations in application to severe knee pain. METHODS: From the CONSTANCES cohort, 62,620 subjects who were working at inclusion and coded were included in the study. The biomechanical job exposure matrix "JEM Constances" was used to assess the intensity/frequency of heavy lifting and kneeling/squatting at work together with work history to characterize the association between occupational exposure and severe knee pain. An innovative model G was developed and evaluated, allowing to compare the accuracy of duration of work and intensity/frequency associations. RESULTS: The mean age was 49 years at inception with 46 percent of women. The G model developed was slightly better than regular models. Among the men subgroup, odds ratios of the highest quartile for the duration and low intensity were not significant for both exposures, whereas intensity/duration were for every duration. Results in women were less interpretable. CONCLUSIONS: Though higher duration increased strength of association with severe knee pain, intensity/frequency were important predictors among men. Exposure estimation along working history should have emphasis on such parameters, though other outcomes should be studied and have a focus on women.


Subject(s)
Musculoskeletal Diseases , Occupational Diseases , Occupational Exposure , Male , Humans , Female , Middle Aged , Musculoskeletal Diseases/epidemiology , Knee Joint , Pain , Odds Ratio , Occupational Diseases/epidemiology
6.
ACS Nano ; 16(9): 14168-14177, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36043881

ABSTRACT

Reconfigurable magnetization textures offer control of spin waves with promising properties for future low-power beyond-CMOS systems. However, materials with perpendicular magnetic anisotropy (PMA) suitable for stable magnetization-texture formation are characterized by high damping, which limits their applicability in magnonic devices. Here, we propose to overcome this limitation by using hybrid structures, i.e., a PMA layer magnetostatically coupled to a low-damping soft ferromagnetic film. We experimentally show that a periodic stripe-domain texture from a PMA layer is imprinted upon the soft layer and induces a nonreciprocal dispersion relation of the spin waves confined to the low-damping film. Moreover, an asymmetric bandgap features the spin-wave band diagram, which is a clear demonstration of collective spin-wave dynamics, a property characteristic for magnonic crystals with broken time-reversal symmetry. The composite character of the hybrid structure allows for stabilization of two magnetic states at remanence, with parallel and antiparallel orientation of net magnetization in hard and soft layers. The states can be switched using a low external magnetic field; therefore, the proposed system obtains an additional functionality of state reconfigurability. This study offers a link between reconfigurable magnetization textures and low-damping spin-wave dynamics, providing an opportunity to create miniaturized, programmable, and energy-efficient signal processing devices operating at high frequencies.

7.
Sci Rep ; 11(1): 15692, 2021 Aug 03.
Article in English | MEDLINE | ID: mdl-34344969

ABSTRACT

We present a new mechanism for manipulation of the spin-wave amplitude through the use of the dynamic charge-mediated magnetoelectric effect in ultrathin multilayers composed of dielectric thin-film capacitors separated by a ferromagnetic bilayer. Propagating spin waves can be amplified and attenuated with rising and decreasing slopes of the oscillating voltage, respectively, locally applied to the sample. The way the spin accumulation is generated makes the interaction of the spin-transfer torque with the magnetization dynamics mode-selective and restricted to some range of spin-wave frequencies, which is contrary to known types of the spin-transfer torque effects. The interfacial nature of spin-dependent screening allows to reduce the thickness of the fixed magnetization layer to a few nanometers, thus the proposed effect significantly contributes toward realization of the magnonic devices and also miniaturization of the spintronic devices.

8.
Nano Lett ; 21(2): 946-951, 2021 Jan 27.
Article in English | MEDLINE | ID: mdl-33231459

ABSTRACT

The interaction between different types of wave excitation in hybrid systems is usually anisotropic. Magnetoelastic coupling between surface acoustic waves and spin waves strongly depends on the direction of the external magnetic field. However, in the present study we observe that even if the orientation of the field is supportive for the coupling, the magnetoelastic interaction can be significantly reduced for surface acoustic waves with a particular profile in the direction normal to the surface at distances much smaller than the wavelength. We use Brillouin light scattering for the investigation of thermally excited phonons and magnons in a magnetostrictive CoFeB/Au multilayer deposited on a Si substrate. The experimental data are interpreted on the basis of a linearized model of interaction between surface acoustic waves and spin waves.

9.
Bioorg Med Chem ; 26(14): 4330-4335, 2018 08 07.
Article in English | MEDLINE | ID: mdl-29716765

ABSTRACT

A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 20 and 1,3-diketone 14 (R = CH2CH2CH2NBu2) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.


Subject(s)
Dronedarone/chemical synthesis , Benzofurans/chemistry , Dronedarone/chemistry , Ketones/chemistry , Molecular Structure , Quinones/chemistry
10.
Sci Rep ; 7(1): 11800, 2017 09 18.
Article in English | MEDLINE | ID: mdl-28924152

ABSTRACT

Gd2(MoO4)3 (GMO) is a well-studied multiferroic material that exhibits full ferroelectric and ferroelastic behavior at room temperature. However, its difficult stabilization in thin films has prevented the study and exploitation of its multiferroic properties in different architectures. Here, we report on the study of GMO thin films deposited on Si(001) substrates by Pulsed Laser Deposition (PLD). The physicochemical properties of the films are discussed and studied. Results obtained by X-ray diffraction, X-ray photoelectron spectroscopy, high resolution transmission microscopy and second harmonic generation show that the orthorhombic (ß'-GMO) multiferroic phase can be stabilized and homogenized by post deposition thermal reconstruction. Finally, the reconstruction process takes place via a complex surface mechanism with a clear leaf-like behavior.

12.
Future Med Chem ; 5(5): 539-51, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23573972

ABSTRACT

JNK is involved in a broad range of physiological processes. Several inflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer's and Parkinson's disease have been linked with the dysregulated JNK pathway. Research on disease models using the relevant knockout mice has highlighted the importance of specific JNK isoformsin-particular disorders and has stimulated further efforts in the drug-discovery area. However, most of the experimental evidence for the efficacy of JNK inhibition in animal models is from studies using JNK inhibitors, which are not isoform selective. Some of the more recent compounds exhibit good oral bioavailability, CNS penetration and selectivity against the rest of the kinome. Efforts to design isoform-selective inhibitors have produced a number of examples with various selectivity profiles. This article presents recent progress in this area and comment on the role of isoform selectivity for efficacy.


Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Animals , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/metabolism
13.
J Med Chem ; 50(23): 5773-9, 2007 Nov 15.
Article in English | MEDLINE | ID: mdl-17948979

ABSTRACT

A novel application of the Gini coefficient for expressing selectivity of kinase inhibitors against a panel of kinases is proposed. This has been illustrated using single-point inhibition data for 40 commercially available kinase inhibitors screened against 85 kinases. Nonselective inhibitors are characterized by Gini values close to zero (Staurosporine, Gini 0.150). Highly selective compounds exhibit Gini values close to 1 (PD184352 Gini 0.905). The relative selectivity of inhibitors does not depend on the ATP concentration.


Subject(s)
Enzyme Inhibitors/chemistry , Phosphotransferases/antagonists & inhibitors , Phosphotransferases/chemistry , Quantitative Structure-Activity Relationship , Adenosine Triphosphate/chemistry
14.
Bioorg Med Chem Lett ; 15(21): 4666-70, 2005 Nov 01.
Article in English | MEDLINE | ID: mdl-16153829

ABSTRACT

Imidazole-based structures of p38 inhibitors served as a starting point for the design of JNK3 inhibitors. Construction of a 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold led to the synthesis of the (S)-enantiomers, which exhibited p38/JNK3 IC50 ratio of up to 10 and were up to 20 times more potent inhibitors of JNK3 than the relevant (R)-enantiomers. The JNK3 inhibitory potency correlated well with inhibition of c-Jun phosphorylation and neuroprotective properties of the compounds in low K+-induced cell death of rat cerebellar granule neurones.


Subject(s)
Mitogen-Activated Protein Kinase 10/antagonists & inhibitors , Protein Kinase Inhibitors/chemical synthesis , Animals , Cell Death/drug effects , Cerebellum/cytology , Imidazoles , Neurons/cytology , Neurons/drug effects , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-jun/metabolism , Rats , Stereoisomerism , Structure-Activity Relationship , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
15.
Prog Med Chem ; 39: 1-72, 2002.
Article in English | MEDLINE | ID: mdl-12536670

ABSTRACT

The striking efficacy of Z-VAD-fmk in the various animal models presented above may reflect its ability to inhibit multiple enzymes including caspases. In accord with this, more selective, reversible inhibitors usually show low efficacy in multifactorial models such as ischaemia, but may offer some protection against NMDA-induced excitotoxicity and hepatitis. Importantly, caspase inhibitors may exhibit significant activity in vivo even when they are applied post insult. As far as the CNS is concerned, the first systemically active inhibitors have emerged. Functional recovery could be achieved in some ischaemia models, but long-term protection by caspase inhibitors is still being questioned. Recent developments in drug design enabled the first caspase inhibitors to enter the clinic. Although initially directed towards peripheral indications such as rheumatoid arthritis, caspase inhibitors will no doubt eventually be used to target CNS disorders. For this purpose the peptidic character of current inhibitors will have to be further reduced. Small molecule, nonpeptidic caspase inhibitors, which have appeared recently, indicate that this goal can be accomplished. Unfortunately, many fundamental questions still remain to be addressed. In particular, the necessary spectrum of inhibitory activity required to achieve the desired effect needs to be determined. There is also a safety aspect associated with prolonged administration. Therefore, the next therapeutic areas for broader-range caspase inhibitors are likely to involve acute treatment. Recent results with synergistic effects between MK-801 and caspase inhibitors in ischaemia suggest that caspase inhibitors may need to be used in conjunction with other drugs. It can be expected that, in the near future, research on caspases and their inhibitors will remain a rapidly developing area of biology and medicinal chemistry. More time, however, may be needed for the first caspase inhibitors to appear on the market.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Caspase Inhibitors , Cysteine Proteinase Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Caspases/physiology , Cysteine Proteinase Inhibitors/chemistry , Drug Design , Humans , Inflammation/drug therapy , Structure-Activity Relationship
16.
Restor Neurol Neurosci ; 14(1): 1-23, 1999.
Article in English | MEDLINE | ID: mdl-12671267

ABSTRACT

Contribution of apoptotic mechanisms to neurodegeneration is an emerging concept. Caspases which are activated during apoptotic cell death may serve as an attractive target of pharmacological intervention. Caspase inhibitors include proteins, peptides, peptidomimetics and various small molecules. Peptide conjugates with quinones, epoxyquinones and epoxyquinols which constitute new types of pharmaeophores exhibit submicromolar activity against caspase-3 and show moderate neuroprotective effects on neuronal cells. Peptide-derived inhibitors may suffer from insufficient cell membrane permeability. However, double ester-type prodrugs may offer an option to transport a peptide-like inhibitor across the cell membrane. These developments may lead to identification of novel neuroprotective drugs.

17.
J Org Chem ; 61(9): 2995-3002, 1996 May 03.
Article in English | MEDLINE | ID: mdl-11667160

ABSTRACT

Both C(2)-P bond breaking and formation in the S-C-P(+) system do not occur according to the antiperiplanar lone pair hypothesis. Experiments using 2-phosphonio derivatives of 5-tert-butyl-1,3-dithiane and cis-4,6-dimethyl-1,3-dithiane are against the participation of higher-energy boat conformers as reactive intermediates. The results obtained support a possibility of conformational adjustment in the course of the reaction. Stereoelectronic control of the C(2)-P bond breaking and formation results from interplay of several factors. The role of the n(S)-sigma(C(2))(-)(P) and sigma(C(4,6))(-)(S)-sigma(C(2))(-)(P) hyperconjugation, as well as of the repulsive interactions between lone electron pairs pi(S) of endocyclic sulfur atoms and pi-electrons of the phenyl ring(s) connected with phosphorus, is discussed.

SELECTION OF CITATIONS
SEARCH DETAIL
...